Original article

Conventional vs. waterjet-assisted endoscopic submucosal dissection in early gastric cancer: a randomized controlled trial

Authors

Ping-Hong Zhou1, Brigitte Schumacher2, Li-Qing Yao1, Mei-Dong Xu1, Thomas Nordmann2, Ming-Yan Cai1, Jean-Pierre Charton2, Michael Vieth3, Horst Neuhaus2

Institutions

1

Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai, China Department of Internal Medicine, Evangelisches Krankenhaus Düsseldorf, Düsseldorf, Germany 3 Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany 2

submitted: 17. August 2013 accepted after revision: 18. May 2014

Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1377580 Published online: 17.9.2014 Endoscopy 2014; 46: 836–842 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X Corresponding author Horst Neuhaus, MD Department of Internal Medicine Evangelisches Krankenhaus Düsseldorf Kirchfeldstrasse 40 40217 Düsseldorf Germany Fax: +49-211-9193960 horst.neuhaus@evkduesseldorf. de

Background and study aims: A hybrid knife was recently developed to allow waterjet-assisted endoscopic submucosal dissection, which aims to speed up and simplify the procedure. This technique has been shown to be effective and safe for the treatment of early gastric cancer (EGC) but it has not yet been compared with conventional ESD. Patients and methods: In this two-center study, patients with an endoscopic and histopathological diagnosis of gastric adenoma or early gastric adenocarcinoma (meeting the extended Japanese criteria for local resection) were randomized to either conventional or waterjet-assisted ESD. The choice of knife was left to the endoscopist in the conventional group whereas the hybrid knife was used in the waterjet group. The primary end point was procedure time, and secondary outcomes included rates of en bloc resection, R0 resection, and complications. Results: A total of 117 patients (mean age 63.0 ± 10.6 years, 76 men) were randomized to either

conventional ESD (n = 59; control group) or waterjet-assisted ESD (n = 58). There were no significant differences in patient demographics or lesion features between the groups. The mean procedure time was significantly shorter in the waterjet group compared with the conventional group (27.5 ± 30.6 vs. 35.0 ± 22.5 minutes; P = 0.0008), and a change of accessories was less frequently required (mean number of changes 1.4 ± 2.0 vs. 23.0 ± 15.4; P < 0.0001). There was no significant difference between the groups in the size of resected specimen, R0 resection rates, number of perforations, major delayed bleedings, or rates of complete remission of neoplasia after 3 months. Conclusions: Waterjet-assisted ESD and conventional ESD are comparably effective and safe techniques for the local treatment of EGC. The waterjet-assisted technique is a faster and simpler procedure and requires fewer accessory changes compared with conventional ESD. ClinicalTrial.gov registration: NCT01943253

Introduction

Western countries seems to be less favorable due to the limited expertise with this challenging technique [4 – 8]. A recently introduced waterjet-assisted ESD system promises to simplify the procedure. This technology allows pressure-controlled injection of fluids through the tip of a HybridKnife (Erbe Elektromedizin GmbH, Tübingen, Germany). Submucosal injection, circumferential cutting, and dissection of lesions, as well as coagulation of bleeding can be performed using the same device without the need to change instruments. These options should result in a faster procedure and may increase the safety and efficacy of ESD [9 – 12]. Our group recently performed two clinical trials on waterjet-assisted ESD in patients with early gastric and esophageal neoplastic lesions [8, 13]. The results confirmed the feasibility of the tech-

!

In Japan and other Asian countries, endoscopic submucosal dissection (ESD) has become the treatment of choice for early gastric cancer (EGC) and is also increasingly used for early esophageal and colorectal neoplasia. This standard or conventional ESD technique was originally developed in Japan [1]. Two recent meta-analyses demonstrated significantly higher rates of en bloc resection and curative resection for ESD compared with endoscopic mucosal resection (EMR) in patients with EGC [2, 3]. However, ESD is more time consuming than EMR and causes more complications, mainly related to perforation and bleeding. The evidence for the clinical value of ESD is still limited and based mainly on data from Japan, which may not be directly applicable to other countries. In particular, the outcome of ESD in

Zhou Ping-Hong et al. Conventional vs. waterjet-assisted endoscopic submucosal dissection … Endoscopy 2014; 46: 836–842

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

836

Original article

Patients and methods !

Objectives of the study The primary objective of the study was to compare the procedure time for the conventional and waterjet-assisted ESD techniques for the endoscopic treatment of EGC. Secondary objectives were to compare the two ESD techniques in terms of rates of en bloc resection and R0 resection of EGC, and the rate of complications.

Study design This prospective, randomized, controlled, two-center clinical study consisted of two arms. The control arm involved the conventional ESD technique using traditional ESD knives such as the IT-2 knife, the DualKnife, and the HookKnife (all Olympus, Tokyo, Japan). The second arm involved the waterjet-assisted technique using the HybridKnife (Erbe). According to sample size estimations, 120 patients were consecutively enrolled in a randomized fashion into the study.

Procedures Technical devices, setting, and agents Diagnostic or therapeutic high-definition gastroscopes were selected at the discretion of the operator and according to the location of the lesion. A 4-mm transparent distance cap was mounted to the tip of the endoscope. The modular VIO 300 D generator (Erbe) was used. In the conventional group, the IT-2 knife (KD611 L, Olympus), the DualKnife (KD-650 L, Olympus), or the HookKnife (KD-620LR, Olympus) were used for circumferential cutting using ENDO CUT Q 2 – 3-3 after submucosal injection, at the discretion of the endoscopist. For dissection DRY CUT E2, 80 W was used. In the waterjet group, the HybridKnife I-type or T-type was used. The HybridKnife combines the capabilities of radiofrequency application and needle-less waterjet injection into one single instrument [9 – 12]. This flexible device, which has an outer diameter of 2.1 mm and a lumen of 120 µm, allows needle-less injection or hydrodissection with a preselected effect setting through a standard working channel of a flexible endoscope. Without changing the instrument, the HybridKnife can be used for marking of the targeted lesion, circumferential cutting, dissection, and coagulation by radiofrequency application. In the current study, the HybridKnife was used in combination with the modular VIO 300 D generator (Erbe) and the waterjet surgical system (ERBEJet 2; Erbe). An isotonic saline solution lightly stained with indigo carmine (2 mL in 250 mL) and mixed with diluted epinephrine (1:250 000) was used for submucosal injection in both ESD groups.

Sedation of patients Patients The inclusion criteria were as follows. Male or female patients aged ≥ 18 years with an American Society of Anesthesiologists health status 1 – 3, and with endoscopic and histopathological diagnosis of gastric adenoma or early gastric adenocarcinoma that met the extended criteria for local resection according to the current guidelines in Japan [14]. The diameter of differentiated mucosal adenocarinoma without ulcer findings was limited to a maximum of 60 mm. Lesions with ulceration were included only if the lesion measured 30 mm or less in diameter. The maximum permitted size of those with an undifferentiated type of mucosal cancer was 20 mm. Exclusion criteria included: pregnancy; coagulopathy (international normalized ratio > 2.0, platelets < 70 × 109/L); evidence of local or distant metastases according to endoscopic ultrasound (EUS) and/or computed tomography (CT) scan; EUS (7.5 MHz probe) findings or endoscopic characteristics indicating tumor infiltration into deep layers of the submucosa or muscularis propria; and patients unfit for deep sedation or general anesthesia. The study protocol was approved by the International Medical and Dental Ethics Commission GmbH in Freiburg, Germany (an institution registered at the Office of Human Research Protections of the United States Department of Health and Human Services and at the German Federal Institute for Drugs and Medical Devices) and by the local ethics commissions (Institutional Review Board approval) of the Zhongshan Hospital, Fudan University, Shanghai, China. The study was performed in compliance with the Declaration of Helsinki and good clinical practice. Written informed consent was obtained from all patients.

In the German center, all endoscopy procedures were performed with the patient under deep sedation following intravenous application of midazolam (2.5 mg) and propofol (bolus 1 mg/kg followed by 300 – 350 mg/kg/h continuous infusion). In the Chinese center, all patients received general anesthesia with tracheal intubation. The parameters were positive end-expiratory pressure (0), tidal volume (8 mL/kg), and frequency (10 bpm, adjusted according to the end-tidal CO2 value).

Preparation of the target area High-resolution video endoscopy (using white light) and chromoendoscopy were used for diagnostic evaluation of the target lesion. The size of lateral tumor expansion was measured using a snare of defined diameter. After measurement, the lesion was marked by coagulation using PULSED APC E2, 20 W. Coagulation markers were applied at a distance of at least 5 mm from the tumor margins.

ESD techniques All procedures were performed exclusively by one of four endoscopists (H.N., B.S. [Germany] and P.H.Z., M.D.X. [China]), each of whom had experience with ESD in experimental and clinical settings. Both German endoscopists had performed at least 40 conventional ESD procedures and had experience of the waterjet-assisted technique prior to the study. P.H.Z. had performed 50 waterjet-assisted and 1000 conventional ESD procedures prior to the study, and M.D.X. had performed 50 and > 500 procedures, respectively. Conventional ESD was carried out as described previously using endoscopy knives and syringes for submucosal injection [1]. " Fig. 1 shows the technical steps of the ESD procedure. In the ● waterjet group, the submucosal injection was performed by the

Zhou Ping-Hong et al. Conventional vs. waterjet-assisted endoscopic submucosal dissection … Endoscopy 2014; 46: 836–842

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

nique in a clinical setting but did not allow a direct comparison with conventional ESD due to the lack of a control group. The aim of the current prospective study, therefore, was to evaluate the procedure time, efficacy, and safety of waterjet-assisted ESD in a randomized controlled comparison with the conventional technique in patients with EGC. The study was performed in two tertiary referral centers in Germany and China, with annual volumes of ESD procedures of approximately 80 and > 1000 cases, respectively.

837

Original article

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

838

Fig. 1 Technical steps of the endoscopic submucosa dissection (ESD) procedure. a Early gastric cancer (type 0-IIa and IIc) at the lesser curvature of the antrum. b Coagulation markers at a distance of approximately 5 mm from the lateral tumor margin. c Circumferential incision of the mucosa at the periphery of the markers using the HybridKnife (T-type; Erbe Elektromedizin GmbH, Tübingen, Germany), following submucosal instillation of saline solution with indigo carmine through the same device. d Complete circumferential incision of the neoplastic lesion. e Dissection of the submucosa using the HybridKnife in a tangential direction to the muscle layer after appropriate lifting of the lesion by submucosal injection. f Resected area after en bloc waterjet-assisted ESD of the targeted lesion including all coagulation markers.

Zhou Ping-Hong et al. Conventional vs. waterjet-assisted endoscopic submucosal dissection … Endoscopy 2014; 46: 836–842

Original article

Statistical analysis The sample size estimation was based on noninferiority of the procedure time at 80 % power and a significance level of 5 % (two sided). The estimated overall sample size was 120 patients (see supplementary material, available online). Randomization was by computer-generated randomization list. Different randomization lists were generated for the two centers (20 patients in Germany, 100 patients in China); therefore, each randomization list was independent of the other.

Data analysis Data were collected and analyzed by means of descriptive statistics (mean and SD) and statistical hypothesis testing. Comparisons between groups were performed by Fisher’s exact test for categorical variables. Independent samples Student’s t tests were used to compare normally distributed and homoscedastic variables between groups, otherwise, the Mann – Whitney test was used. P values of < 0.05 were considered to be statistically significant. The study data were analyzed in the framework of the per-protocol analysis. Main outcome measurements (procedure time and instrument replacement) were also analyzed through intentionto-treat analysis.

Preparation and histopathological evaluation The resection specimen was pinned onto cork. The maximum horizontal expansion was measured, and the specimen was fixed in 4 % neutral buffered formalin and sent for histopathological evaluation. Diagnostic criteria of the World Health Organization classification of gastrointestinal tumors 2010 were applied [15]. No different classifications were used in either country.

Follow-up Patients were hospitalized for at least 3 days after ESD. Secondlook gastroscopy was conducted 1 or 2 days after the procedure to exclude delayed bleeding and to investigate the resected area for residual superficial vessels. At 30 days after the procedure, patients were interviewed via telephone for evaluation of complaints and delayed complications. Re-evaluation of the ESD scar for residual or recurrent neoplasia was performed 3 month after the procedure.

Definitions of outcome En bloc resection was defined as resection of the target lesion, including coagulation markers, in one piece. Histologically complete resection (R0) was defined as en bloc resection and histological confirmation of horizontal and vertical margins that were free of neoplasia. Histologically incomplete resection was defined as tumor infiltrated (R1) or undetermined (RX) margins of the resected specimen. Treatment failure was defined as incomplete resection or if the procedure remained incomplete because of complications. Perforation was defined as an endoscopically visible hole in the gastric wall and/or postprocedural clinical signs of peritonitis due to perforation. Bleeding was registered if an oozing or spurting bleeding could not be managed by short bursts of coagulation with the tip of the endoscopy knife, thus requiring alternative endoscopic intervention by use of coagulation forceps or hemoclips. Complete remission of neoplasia was defined as histologically complete resection (R0), or incomplete resection (R1 or RX) with one follow-up endoscopy including biopsies from the resection scar that indicated no residual neoplasia.

Results !

A total of 120 consecutive patients with EGC or adenoma were enrolled into the study between May 2011 and July 2012. Three patients were not included in the analysis: in one patient the lesion was too small to be considered for ESD according to the inclusion criteria, and two other patients required surgical intervention because initial ESD revealed a more advanced tumor stage with obvious massive submucosal cancerous invasion. Of the remaining 117 patients (per-protocol population), 59 were randomized to conventional ESD and 58 to the waterjet-assisted technique. The flow chart of patient enrollment is shown in " Fig. 2. The baseline characteristics of patients are summarized ● " Table 1. in ● All waterjet-assisted ESD resections were performed in an en bloc fashion; one resection in the 59 conventional ESD procedures could not be achieved in one piece (P = 1.0). In the perprotocol analysis, the mean procedure time (primary objective) was 27.5 ± 30.6 minutes in the waterjet group and 35.0 ± 22.5 minutes in the conventional group (P = 0.0008), which represents a reduction in the procedure time of more than 20 % when using the waterjet-assisted technique. Instrument exchange was required a mean of 1.4 ± 2.0 times in the waterjet

120 patients 2 drop-outs

20 Germany

100 China

(Surgical intervention necessary)

1 drop-out (Lesion size does not fit the inclusion criteria)

117 patients 58 Waterjet

Fig. 2

100 Conventional’

Flow chart of patient enrollment.

Zhou Ping-Hong et al. Conventional vs. waterjet-assisted endoscopic submucosal dissection … Endoscopy 2014; 46: 836–842

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

HybridKnife. The waterjet effect setting can be incremented in 10-bar steps according to the effect required. The number of injections used and the total volume of fluid were documented. Visible vessels with an estimated diameter of < 1.5 mm were coagulated using the ESD knife using FORCED COAG E2, 60 W. Larger vessels were coagulated using forceps (Coagrasper; Olympus Medical Systems Co., Tokyo, Japan) or hot biopsy forceps using SOFT COAG E5, 80 W. At all stages of ESD, the HybridKnife could be exchanged for another type of knife if technical difficulties occurred or there was insufficient control. Endoscopically visible perforations during the procedure were closed by hemoclips. Procedural bleedings were treated with coagulation via the HybridKnife or one of the conventional ESD knives; coagulation forceps or hemoclips were used in cases of failure. The intervention was abandoned and the patient was transferred to surgery if the complete resection could not be achieved due to anatomical or technical difficulties. The procedure time was taken at the end of complete resection or at procedural failure. After endoscopic removal of the specimen, the resected area was evaluated for residual superficial vessels, which were coagulated using the endoscopy knife or, if necessary, with a coagulation forceps.

839

Original article

Patients, n

Conventional

Waterjet-

ESD

assisted ESD

59

58

50

49

9

9

Center, no. of patients

P

1.00

Shanghai Düsseldorf

Table 2 Histology of the resected specimen (per-protocol population n = 117).

Waterjet-

ESD

assisted ESD

Patients, n

59

58

Adenocarcinoma

36

38

5

3

sm1 1 sm2, sm3 2

P

0.70

1

2

15

16

0.84

Indefinite for neoplasia

7

1

0.06

Negative for neoplasia

1

3

0.36

Adenoma

Sex, n

Conventional

Male

37

38

Female, n

22

20

0.85

65.7 ± 10.7

61.8 ± 10.4

0.14

Antrum

34

34

ESD, endoscopic submucosal dissection. 1 sm1 = infiltration of the submucosa of ≤ 500 µm. 2 sm2, sm3 = infiltration of the submucosa of > 500 µm.

Body

17

21 0.80

sia. Re-review of the histological changes of the resected specimen showed regenerative lesions only (so called pseudo-carcinomatous epithelium). Eight cases with prior diagnosis of gastric high grade dysplasia were diagnosed as indefinite for dysplasia. These slides were also re-reviewed after resection and the diagnosis was downgraded to marked regenerative changes (pseudocarcinomatous). The R0 resection rates of the neoplastic or indefinite neoplastic lesions were 94.5 % (52/55) in the waterjet-assisted group and 89.7 % (52/58) in the conventional group (P= 0.49). The size of the specimen, as determined by planimetry, was 1289 ± 681 mm2 for those resected by the waterjet-assisted technique and 1240 ± 684 mm2 following conventional ESD (P = 0.47). Histology revealed cancerous infiltration of the submucosa in five patients from the waterjet group and six patients from the conventional " Table 2). Surgery was recommended for the group (P= 0.75) (● three patients with submucosal infiltration deeper than 500 µm. Follow-up indicated a 30-day mortality rate of zero in both groups. Eight patients (five waterjet, three conventional) could not be considered for 3 month follow-up because they had either undergone surgery because of advanced tumor stages or were lost to follow-up. Telephone calls revealed no complaints or delayed complications within 30 days. The 3-month follow-up revealed no delayed complication in either group. Endoscopic surveillance documented complete remission of neoplasia in 52/58 in the waterjet group and in 56 /59 patients in the conventional group according to the intention-to-treat analysis, corresponding to complete local resection rates of 89.7 % and 94.9 %, respectively (P = 0.32).

Age, mean ± SD, years Location of lesion, n

Fundus or cardia

8

Size of lesion, mean ± SD, mm 2

672 ± 439

3 630 ± 403

ESD, endoscopic submucosal dissection.

group and 23.0 ± 15.4 times in the conventional group (P < 0.0001). In intention-to-treat analysis, the procedure time and instrument exchange differed only slightly: mean procedure time 27.9 ± 30.4 minutes (waterjet group) and 35.0 ± 22.5 minutes (conventional group; P = 0.0013); instrument exchanges 1.5 ± 2.0 (waterjet group) and 22.7 ± 15.5 (conventional group; P < 0.0001). The main outcomes (operation time and instrument change) are shown in " Fig. 3. Furthermore, the results of procedure time and switch ● to coagulation forceps were comparable between the distal and proximal stomach. Three perforations (one waterjet, two conventional) occurred during ESD and were closed by clip placement. Switch to a conventional ESD knife in the waterjet group was not required. Switch to coagulation forceps for hemostasis occurred in a mean of 0.95 ± 1.66 cases in the waterjet group and in 2.86 ± 3.81 cases in the conventional group (P = 0.0009). No other complications were recorded during the procedures. Within 72 hours postoperatively, minor delayed bleedings were recorded in four patients in the waterjet group and seven patients in the conventional group (P = 0.53). In addition, there was one major delayed bleeding in the conventional ESD group, which was managed endoscopically. Histology of the resected specimen was negative for neoplasia in three cases in the waterjet group and in one case in the conven" Table 2). The histological diagnoses tional ESD group (P= 0.36) (● in these four ESD procedures was active helicobacter gastritis with foveloar hyperplasia but no neoplastic lesion. The diagnosis from biopsy prior to ESD was high grade intraepithelial neopla-

80 Instrument replacement

60

40

20

0

Fig. 3 Main results of the study: procedure time and number of instrument exchanges required.

50 40 30 20 10 0 Waterjet

Conventional

Waterjet

Conventional

Zhou Ping-Hong et al. Conventional vs. waterjet-assisted endoscopic submucosal dissection … Endoscopy 2014; 46: 836–842

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

Table 1 Baseline characteristics of patients (per-protocol population n = 117).

Procedure time [minutes]

840

Discussion !

In this study, the mean procedure time for waterjet-assisted ESD was about 20 % shorter than the procedure time for conventional ESD. Simultaneously, the waterjet-assisted technique required fewer instrument exchanges because the change to syringe for submucosal injection could be completely omitted. Safety and efficacy parameters were comparable between the groups. Several Japanese studies have shown excellent results of ESD for EGC, with en bloc resection rates significantly higher in patients who met the guideline criteria compared with those with extended criteria, but overall survival was statistically similar [16 – 19]. These results need to be confirmed internationally, which is difficult, particularly in Europe due to both the low number of detected cases of EGC and the limited experience with ESD [20]. Only a few Western case series or feasibility trials on gastric ESD have been performed in more than a single center; to date, no trial has enrolled more than 100 cases [4 – 8]. Efficacy and safety in these Western series were inferior to most of the Japanese trials, with reported R0 resection rates of 50 % – 92 %, mean procedure duration of 74 – 157 minutes, and complication rates of 5 % – 50 %. Improvement can be expected from participation of specialized endoscopists in structured training courses and limitation of ESD to specialist referral centers [21]. In addition, simplification of the complex ESD technique should result in a quicker procedure and increase the acceptance of the technique as a minimally invasive alternative to surgery. In this context, we recently reported on the first clinical trial of waterjet-assisted ESD in patients with EGC [8]. The waterjet system allows pressure-controlled injection of fluids through the tip of the recently developed HybridKnife. Submucosal injection, circumferential cutting, and dissection of lesions, as well as coagulation of bleeding sources can be performed with the same device without the need for instrument exchange. These options should speed up the procedure and may increase its safety and efficacy. The prospective clinical study included 29 patients with EGC. En bloc resection was achieved in 90 % of cases, median procedure time was 74 minutes, 30-day morbidity was 13.8 %, and R0 resection rate was 64 %. Surgery was not required for the management of complications. All but one resection achieved vertical neoplasia-free tumor margins. The results of this first trial and previous series on waterjet-assisted ESD by our group and other institutions encouraged us to perform the first randomized controlled trial to compare the technique with conventional ESD for EGC. Procedure time was chosen as the primary objective because it should be related to the complexity of the procedure and the skill of the operator. A long procedural time is frequently considered as an argument against ESD in Western countries because of increasing costs and inappropriate reimbursement. There is also a patient safety risk with the increased anesthesia time required. However, according to a recent survey, even a multicenter trial would not be able to recruit 120 cases in Europe alone [22]. Therefore, we agreed on a two-center trial, which included a Chinese tertiary referral center with extensive expertise in various ESD techniques, and a German center with more limited experience in both the waterjet-assisted technique and conventional ESD. Recording of the procedure time started after the lesion has been marked because all steps to this point are identical for both ESD techniques. This means that the procedure time in the current study is not directly comparable to the overall procedure time in

many other studies on ESD. Overall, 60 % of all lesions were located in the gastric antrum, which is considered to be the easiest location for ESD. This favorable selection may have contributed to the promising results of the current trial. It may also explain the short mean procedure time of 35 minutes in the conventional group, which was significantly less (28 minutes) in the waterjet group. This difference seems to have had a limited impact on the clinical outcomes of ESD, but shortening the procedure time by 20 % would be relevant in longer procedures, particularly those performed by less experienced operators. In addition, the waterjet-assisted technique simplifies the procedure because significantly fewer instrument exchanges are required compared with conventional ESD. Both ESD techniques showed excellent results and all but one resection could be performed in an en bloc fashion. The R0 resection rates of 90 % in the conventional group and 95 % in the waterjet group were not statistically different. Similar rates were reported in large prospective Japanese series [17]. In addition, there was no significant difference in terms of complications, and the 3-month intention-to-treat follow-up data indicated complete local resection rates of 95 % and 90 % in the conventional and waterjet groups, respectively. Limitations of the current study are that the procedures were performed by only four operators. The operators could have been biased in favor of one technique (e. g. in speed of interventions or request for changes of accessories). In addition, different results may be obtained when ESD is performed at the beginning of the learning curve, during which the advantages of the HybridKnife should be even more obvious. The study was focused on the ESD technique and short-term results. In the conventional group, several strategies and knives were used; thus, this group was not a homogeneous group. Despite the broad choice of instruments, safety and efficacy were not superior to those in the waterjet group, which used the HybridKnife alone. Another limitation of the study is that the center in Shanghai included 85 % of all patients, which corresponds to the differences between East and West both in terms of the incidence of early gastric carcinoma and the larger population in China compared with Germany. The primary analysis of the study data was the per-protocol analysis. The overall drop-out rate across both centers was only 3 /120 (2.5 %), and therefore there was only a small difference between the per-protocol and intention-to-treat analyses. The main outcome parameters (operation time and instrument exchange) were reported for both analyses. The procedure times for the conventional technique and the waterjet-assisted technique were longer in the German center than in the Chinese center. Because there were only 18 analyzable patients in the German study group, it was decided to present only the overall procedure time for each intervention, as a sample size of 18 was too small to show a significant difference between the waterjet and conventional techniques in the German group vs. the Chinese group. The experience with both conventional and waterjet-assisted ESD techniques is much higher in Chinese centers and the learning curves of both techniques are quite flat. In the current study, a clear benefit of waterjet-assisted ESD can only be demonstrated for the experienced endoscopist. We believe that there is also a benefit for the less-experienced endoscopist but this could not be shown due to the small sample size of only 18 patients in the WESD group. The histopathological analysis of the resected specimen and the 3-month follow-up data indicate that both ESD methods can be considered as curative treatment in approximately 90 % of pa-

Zhou Ping-Hong et al. Conventional vs. waterjet-assisted endoscopic submucosal dissection … Endoscopy 2014; 46: 836–842

841

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

Original article

Original article

tients. However, as with other endoscopic resection methods, long-term follow-up is required for early detection of tumor recurrence or metachronous neoplasia. The strength of this trial is that it represents the first prospective randomized controlled trial on different ESD techniques in humans. Two referral centers participated; although the Chinese center enrolled the vast majority of cases, the trial demonstrates that ESD can be performed in a Western institution with similar results in spite of less expertise. The waterjet-assisted ESD technique performed very well in the Chinese high-volume center but also showed good results in the German center even though experience was more limited. Thus, the waterjet-assisted ESD seems to be a helpful procedure for European endoscopy centers. Competing interests: Both study centers received research funding from Erbe Elektromedizin GmbH, Tübingen, Germany to conduct this study.

References 1 Gotoda T. A large endoscopic resection by endoscopic submucosal dissection procedure for early gastric cancer. Clin Gastroenterol Hepatol 2005; 3: 71 – 73 2 Cao Y, Liao C, Tan A et al. Meta-analysis of endoscopic submucosal dissection versus endoscopic mucosal resection for tumors of the gastrointestinal tract. Endoscopy 2009; 41: 751 – 757 3 Lian J, Chen S, Zhang Y et al. A meta-analysis of endoscopic submucosal dissection and EMR for early gastric cancer. Gastrointest Endosc 2012; 76: 763 – 770 4 Neuhaus H, Costamagna G, Deviere J et al. Endoscopic submucosal dissection (ESD) of early neoplastic gastric lesions using a new doublechannel endoscope (the “R-scope”). Endoscopy 2006; 38: 1016 – 1023 5 Catalano F, Trecca A, Rodella L et al. The modern treatment of early gastric cancer: our experience in an Italian cohort. Surgical endoscopy 2009; 23: 1581 – 1586 6 Dinis-Ribeiro M, Pimentel-Nunes P, Afonso M et al. A European case series of endoscopic submucosal dissection for gastric superficial lesions. Gastrointest Endosc 2009; 69: 350 – 355 7 Probst A, Pommer B, Golger D et al. Endoscopic submucosal dissection in gastric neoplasia – experience from a European center. Endoscopy 2010; 42: 1037 – 1044

8 Schumacher B, Charton JP, Nordmann T et al. Endoscopic submucosal dissection of early gastric neoplasia with a water jet-assisted knife: a Western, single-center experience. Gastrointest Endosc 2012; 75: 1166 – 1174 9 Kaehler GF, Sold MG, Fischer K et al. Selective fluid cushion in the submucosal layer by water jet: advantage for endoscopic mucosal resection. Eur Surg Res 2007; 39: 93 – 97 10 Schumacher B, Neuhaus H, Enderle MD. Experimental use of new device for mucosectomy. Acta Endoscopica 2007; 37: 673 – 678 11 Neuhaus H, Wirths K, Schenk M et al. Randomized controlled study of EMR versus endoscopic submucosal dissection with a waterjet hybrid-knife of esophageal lesions in a porcine model. Gastrointest Endosc 2009; 70: 112 – 120 12 Yahagi N, Neuhaus H, Schumacher B et al. Comparison of standard endoscopic submucosal dissection (ESD) versus an optimized ESD technique for the colon: an animal study. Endoscopy 2009; 41: 340 – 345 13 Neuhaus H, Terheggen G, Rutz EM et al. Endoscopic submucosal dissection plus radiofrequency ablation of neoplastic Barrett’s esophagus. Endoscopy 2012; 44: 1105 – 1113 14 Gotoda T. Endoscopic resection of early gastric cancer: the Japanese perspective. Curr Opin Gastroenterol 2006; 22: 561 – 569 15 Bosman FT, Carneiro F, Hruban RH et al. eds. WHO classification of tumours of the digestive system. 4th edn. Lyon, France: IARC Press; 2010 16 Yamaguchi N, Isomoto H, Fukuda E et al. Clinical outcomes of endoscopic submucosal dissection for early gastric cancer by indication criteria. Digestion 2009; 80: 173 – 181 17 Isomoto H, Shikuwa S, Yamaguchi N et al. Endoscopic submucosal dissection for early gastric cancer: a large-scale feasibility study. Gut 2009; 58: 331 – 336 18 Hitomi G, Watanabe H, Tominaga K et al. Endoscopic submucosal dissection in 100 lesions with early gastric carcinoma. Hepatogastroenterology 2009; 56: 254 – 260 19 Gotoda T, Iwasaki M, Kusano C et al. Endoscopic resection of early gastric cancer treated by guideline and expanded National Cancer Centre criteria. Br J Surg 2010; 97: 868 – 871 20 Ribeiro-Mourao F, Pimentel-Nunes P, Dinis-Ribeiro M. Endoscopic submucosal dissection for gastric lesions: results of an European inquiry. Endoscopy 2010; 42: 814 – 819 21 Deprez PH, Bergman JJ, Meisner S et al. Current practice with endoscopic submucosal dissection in Europe: position statement from a panel of experts. Endoscopy 2010; 42: 853 – 858 22 Neuhaus H. Endoscopic submucosal dissection in the upper gastrointestinal tract: present and future view of Europe. Dig Endosc 2009; 21: 4 – S9

Supplementary material online content viewable at: www.thieme-connect.de

Zhou Ping-Hong et al. Conventional vs. waterjet-assisted endoscopic submucosal dissection … Endoscopy 2014; 46: 836–842

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

842

Copyright of Endoscopy is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.

Conventional vs. waterjet-assisted endoscopic submucosal dissection in early gastric cancer: a randomized controlled trial.

A hybrid knife was recently developed to allow waterjet-assisted endoscopic submucosal dissection, which aims to speed up and simplify the procedure. ...
532KB Sizes 0 Downloads 6 Views